Project Summary Overall goals of the proposed work: The human prostate gland is enlarged with age. The molecular mechanisms that lead to this age-related re-growth of the prostate are essentially unknown. The objective of the proposed research is to study the mechanism underlying initiation of the age-related re-growth of the prostate. We found that the protein (WDR77) in the cytoplasm is essential and sufficient to drive growth of prostate cells at the early stage of prostate development. The WDR77-driven cell growth is ceased in adult prostate but the WDR77-driven cell growth is re-activated during prostate aging process. As the consequence of this event, the age-related cell growth is initiated. Aim 1 will study how the WDR77 gene is re-activated in stromal cells in the aging prostate. The proposed research in Aims 2 and 3 will investigate the molecular mechanisms by which WDR77 promotes cellular proliferation. Significance of the proposed research: Our studies identify a novel mechanism by which WDR77 contributes to the age-related prostate growth. The proposed research will investigate how WDR77 is re-activated in aging prostate and the mechanisms by which WDR77 drives cell growth. This study represents a novel study concept that relates to the basic biology of prostate aging. The study will not only help to understand the basic biology of prostate aging and provide a novel strategy but also prevent the development of various prostatic diseases by specifically inhibiting the age-relate re-growth of the prostate in old men. Thus, the proposed research fits to the NIA's mission -- To help improve the health and well-being of old people through research.